A diabetic foot ulcer (DFU) is a serious complication in patients with diabetes mellitus (DM). A DFU is the most common cause of non-traumatic limb amputation, and patients with DFUs have increased mortality rates within 5 years after amputation. DFUs also increase the risk of cardiovascular and cerebrovascular diseases; therefore, with the increasing incidence and prevalence of diabetic foot wounds, DFUs are gradually becoming a major public health problem. The pathophysiology of DFUs is complicated and remains unclear. In recent years, many studies have demonstrated that the pathophysiology of DFUs is especially associated with neuropeptides, inflammation, and biofilms. Neuropeptides, especially substance P (SP) and calcitonin gene-related peptide (CGRP), play an important role in wound healing. SP and CGRP accelerate the healing of cutaneous wounds by promoting neovascularization, inhibiting the release of certain proinflammatory chemokines, regulating macrophage polarization, and so on. However, the expression of SP and CGRP was downregulated in DM and DFUs. DFUs are characterized by a sustained inflammatory phase. Immune cells such as neutrophils and macrophages are involved in the sustained inflammatory phase in DFUs by extracellular traps (NETs) and dysregulated macrophage polarization, which delays wound healing. Furthermore, DFUs are at increased risk of biofilm formation. Biofilms disturb wound healing by inducing a chronic inflammatory response, inhibiting macrophage phagocytosis and keratinocyte proliferation migration, and transferring antimicrobial resistance genes. To understand the relationships among neuropeptides, inflammation, biofilms, and DFUs, this review highlights the recent scientific advances that provide possible pathophysiological insights into the delayed healing of DFUs.

中文翻译：

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神经肽、炎症、生物膜和糖尿病足溃疡

糖尿病足溃疡 (DFU) 是糖尿病 (DM) 患者的严重并发症。DFU 是非创伤性截肢的最常见原因，DFU 患者在截肢后 5 年内死亡率增加。DFUs还会增加心脑血管疾病的风险；因此，随着糖尿病足部伤口发病率和患病率的增加，DFUs逐渐成为主要的公共卫生问题。DFUs的病理生理学很复杂，目前尚不清楚。近年来，许多研究表明，DFUs的病理生理学尤其与神经肽、炎症和生物膜有关。神经肽，尤其是 P 物质 (SP) 和降钙素基因相关肽 (CGRP)，在伤口愈合中起重要作用。SP和CGRP通过促进新生血管形成、抑制某些促炎趋化因子的释放、调节巨噬细胞极化等来加速皮肤创面的愈合。然而，SP 和 CGRP 的表达在 DM 和 DFU 中下调。DFU 的特点是持续的炎症期。中性粒细胞和巨噬细胞等免疫细胞通过细胞外陷阱 (NETs) 和失调的巨噬细胞极化参与 DFU 的持续炎症阶段，从而延迟伤口愈合。此外，DFU 形成生物膜的风险增加。生物膜通过诱导慢性炎症反应、抑制巨噬细胞吞噬作用和角质形成细胞增殖迁移以及转移抗菌素抗性基因来干扰伤口愈合。要了解神经肽之间的关系，